A novel open‐source software‐based high‐precision workflow for target definition in cardiac radioablation

Noninvasive ablative radiotherapy of cardiac arrhythmias (stereotactic ablative body radiation) has shown promising initial results. Precise targeting of the arrhythmogenic substrate is paramount to limit adverse effects to healthy myocardium, organs at risk, and cardiac implantable electronic devices. Using electroanatomic maps for treatment planning is technically challenging.


| Radiotherapy planning CT
With the patient in an immobilization device (Bodyfix; Elekta AB, Stockholm, Sweden) a noncontrast, nongated chest CT with a skin-to-skin field of view was acquired for radiotherapy planning (Somatom AS; Siemens, Forchheim, Germany). In addition, a contrastenhanced cardiac CT was performed with ECG-gating to 70% of the RR interval (diastolic phase).

| Import and 3D registration of electroanatomic maps
Radiotherapy planning is performed in the space of the planning CT.
Spatial registration of the electroanatomic map into the CT coordinates is, therefore, a crucial step in the treatment planning workflow based on electrophysiological data. Data export in different cardiac mapping systems differs and export formats are sparsely documented. We, thus, analyzed data files exported or archived from the mapping workstations. Through manual inspection of binary raw data, comparison of the file structure to established standard formats, and meticulous correlation of data displayed on the workstation to the exported data stream we were able to reverse engineer significant parts of the undocumented export/archive file formats. RHYTHMIA HDx (Boston Scientific, St. Paul, MN, USA) currently lacks dedicated export functionality, but studies can be archived on external storage media for backup and later review. The archive file format is undocumented but seems to be nonstandard XML files containing binary data. Fields holding the triangulated mesh and electric information have been identified in the file format and this information can thus be extracted.
A plug-in for 3D Slicer, EAMapReader, has been written which reads maps exported from these three mapping systems. We have made EAMapReader (including its source code) available at https:// github.com/stephan1312/SlicerEAMapReader.

| Software architecture
Upon installation of EAMapReader through the 3D Slicer application, the plug-in registers as a so-called scripted module which is seamlessly integrated into the existing user interface. The plug-in has been written in the interpreted Python programming language and, therefore, runs on all platforms supported by 3D Slicer (Windows, Mac OS, and various Linux distributions). EAMapReader parses the data exported or archived from the mapping workstation and recreates the map as a triangulated mesh with overlaid scalar information (voltage and LAT). This allows 3D Slicer's powerful built-in visualization capabilities and analysis tools to be used with the map. | 2691 index: 600), but the VT remained inducible. An epicardial or midventricular origin was suspected based on the voltage and the pace mapping results, as well as the VT morphology. 8 Since epicardial access was limited after prior cardiac surgery the patient was offered cardiac SABR as an individual treatment trial and informed consent was obtained. Following planning and treatment as described below the CIED showed unchanged sensing amplitudes, pacing thresholds, and impedances. No acute toxicity was observed. However, a different VT with a tachycardia cycle length of 380 ms recurred in the first weeks after treatment and the patient underwent another invasive study 2 months after radiation treatment. The treated VT morphology was no longer inducible, but a different VT (inferior axis, left bundle branch block configuration) was successfully ablated from the right ventricular outflow tract using irrigated RF ablation. No recurrences were observed since then with a total follow-up of 5 months.

| Accuracy metrics
We calculated various accuracy metrics to estimate errors introduced by the registration of the electroanatomic map to the CT.
The mean pointwise distance of the CARTO map to the LV endocardial surface on the CT was 3.1 mm after ICP registration, with the 95th percentile of 8.3 mm. The Dice similarity coefficient (DSC) is a metric for the spatial similarity of two 3D structures, with values ranging from 0 for non-overlapping structures to 1 for identical, fully overlapping structures. 9 We obtained a DSC of 0.83 between the CARTO map of the LV and the corresponding CT endocardial surface, indicating very good agreement.

| DISCUSSION
We propose a high-precision targeting workflow for stereotactic ablation of ventricular arrhythmias based on invasively obtained electroanatomic information. We created software that enables the import and analysis of electroanatomic maps from three widely used clinical mapping systems and validated it with real-world clinical data from the CARTO system. natively in the CT coordinate system, and the transfer of ECGi-derived target locations to the planning CT is trivial. 11 Spatial accuracy of ECGi, however, is limited and depends on a number of factors. Septal activation, for example, is inherently difficult to represent on the epicardial surface. 11 Furthermore, epicardial exit sites as delineated by ECGi have been shown to be spatially distant from the diastolic isthmus in ischemic VT in humans. 12 Invasive electroanatomic mapping has been shown to achieve high spatial resolution and accuracy, and high-definition acquisition of electrical signals facilitates the detection of conducting channels in areas of the scar. 13 The proposed workflow unlocks this highprecision data to be used for planning SABR treatments of cardiac arrhythmias. We were able to align the CARTO map to the planning CT within a few millimeters, thus enabling an accurate transfer of map-derived locations to the planning CT.
Quality of alignment (registration distance) between different modalities is affected by cardiac and respiratory motion. The respiratory motion moves the whole heart in the chest and can be addressed by rigid transformations of the electroanatomic map.
Differences in the cardiac cycle are more problematic but can be overcome by the acquisition of a diastolic phase cardiac CT. However, depending on the quality of the imaging and the map, resulting registration distances might be larger than in the present data.
All components specific to this workflow are freely available, opensource, and platform-independent. 3D Slicer has been created over the last two decades by a worldwide community of developers mainly through support from the US National Institutes of Health. The software has been used for image analysis and visualization in hundreds of scientific applications, from automated image segmentation to surgical navigation. 5 Likewise, the SlicerRT extension has been validated extensively for radiotherapy research. 6,14 Our module, EAMapReader, is freely available for download and its streamlined design can easily be extended further if the need for new features arises.
Just a few weeks ago a similar approach has been published, using MATLAB and 3D Slicer. 15 While providing similar capabilities in reading CARTO maps, our workflow is seamlessly integrated into 3D Slicer as a plug-in and does not depend on proprietary MATLAB software. Also, EAMapReader reads Ensite and RHYTHMIA maps in addition to CARTO. 16

| Limitations
Stereotactic radioablation of cardiac arrhythmias is still a novel technique and patient numbers are limited. In the present paper, we propose a novel high-precision target definition workflow and report a patient case as proof of concept, but no larger-scale clinical trial has been performed.
Thus, it is unclear whether high-precision planning based on electroanatomic maps is superior to ECGi-based target identification or "eyeballing" with regard to ablation outcomes and adverse events. Although the import of map data exported from the EnSite and RHYTHMIA systems is feasible with our software and has been tested with sample data, no clinical validation has been performed yet.
Furthermore, a limitation in radioablation of VT is that easy inducibility of one VT might mask other VT substrate at the time of the diagnostic study. This is different from RF ablation with sequential VT induction, ablation, and induction of the next VT followed by ablation in a single session. In the clinical case presented as an illustration of our workflow, a second VT was never seen at the initial invasive study since the index VT was so easily inducible. Only after radioablation of the first VT this second morphology became clinically relevant and was successfully ablated in a second RF ablation session. This underscores that that radiation target choice is a complex process and further studies are needed to establish robust criteria to target cardiac tissue for radiation therapy.

| CONCLUSION
We proposed a novel high-precision target definition workflow for stereotactic ablation of cardiac arrhythmias and demonstrated it in a patient case. Multimodal integration of the electroanatomic map with the planning CT allows for highly accurate localization of previously identified electrophysiological features in CT space. The alignment of the electroanatomic map with corresponding structures on the CT was within a few millimeters when used with real-world clinical data. In the present study, we developed the workflow and the necessary software tool and made it freely available. It remains to be shown whether this novel planning workflow leads to superior ablation outcomes when compared with other approaches.